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Collaboration “DUBbed” a success
CAMBRIDGE, U.K.—A collaboration that began in November 2018 between Mission Therapeutics and AbbVie has reached its first significant milestone with the identification of several deubiquitylating enzymes (DUBs) as potential drug targets. AbbVie has selected a panel of DUBs that will be advanced into further characterization and screening activities.
The collaboration is focused on the identification of specific DUBs and inhibitor compounds as potential treatments for Alzheimer’s disease and Parkinson’s disease. The agreement gives AbbVie the option to secure exclusive rights to develop and commercialize DUB inhibitors against up to four selected targets, with Mission standing to receive success-based milestone payments and royalty payments for each successfully commercialized product. According to Dr. Anker Lundemose, Mission’s CEO, the next stage of this collaboration consists of additional target validation and “a move into the discovery of small-molecule inhibitors of the DUB targets.”
“Partnering with AbbVie has been a great experience and instrumental for our research. AbbVie brings expertise and capabilities complementary to our own, and it is a testament to all involved that we have reached this important milestone,” Lundemose said in a press release. “We have made good progress to-date and our high-quality data has enabled AbbVie to take the decision to select multiple DUBs for further investigation. We look forward to continuing to work together to discover and develop DUB inhibitors towards the treatment of Alzheimer’s and Parkinson’s diseases.”
As explained on Mission’s website, “DUBs comprise a group of around 100 human proteins that play important roles in regulating ubiquitylation, the process where ubiquitin—a small regulatory protein so called because it is present in all complex organisms and virtually every cell in the body—controls protein homeostasis, protein activity, intracellular location, and sub-cellular turnover or degradation.” As both Alzheimer’s disease and Parkinson’s disease are typified by the overabundance of misfolded or toxic proteins, DUBs’ ability to regulate the degradation of such proteins could make them promising candidates within these diseases.
“DUBs represent a potential novel class of drug target. The collaboration with AbbVie is structured to utilize Mission’s DUB platform to identify novel DUB drug targets for AD and PD, and the subsequent development of innovative small-molecule drugs,” Lundemose tells DDNews. “To Mission’s knowledge, this is the first systematic approach to identify novel DUB drug targets for these two debilitating diseases, for which there are currently no disease-modifying treatments.”
According to current estimates, some 10 million individuals worldwide have Parkinson’s disease, and roughly 50 million individuals suffer from dementia and Alzheimer’s disease. While advancements are being made in terms of the pathology of these diseases, those numbers are on the rise, particularly in the case of Alzheimer’s disease. Alzheimer’s Disease International forecasts that the number of individuals with Alzheimer’s “will almost double every 20 years, reaching 75 million in 2030 and 131.5 million in 2050. Much of the increase will be in developing countries.” An individual’s likelihood of developing either of these neurodegenerative diseases increases with age, and as people live longer and aging populations continue to grow, the market need for effective therapeutics is severe.
“The numbers of people living with Alzheimer’s and Parkinson’s is growing and there are currently no treatments capable of stopping or reversing either disease’s progression. This collaboration, using Mission’s DUB technology platform, shows promise for identifying potential drug targets and the development of new therapeutic options. We look forward to advancing our drug discovery programs with our Mission colleagues,” commented Dr. Eric Karran, vice president, Discovery Neuroscience Research, AbbVie.
Mission’s spokesperson says the company is exploring the potential of DUBs in a variety of other indications in addition to neurodegenerative disease, such as kidney disease, fibrosis and rare mitochondrial diseases. One of the key targets in their pipeline is USP30, a mitochondrial-associated DUB that plays a role in the aforementioned disease indications.
As for any additional partnering efforts by the company, Lundemose notes that “This is a fast-emerging area of interest in the pharmaceutical industry broadly. Mission believes that it has the leading DUB inhibitor platform in the industry and, as a consequence, is involved in several exploratory collaboration discussions with other companies across therapeutic areas.”